New Directions in CSF Outflow Research

New Directions in CSF Outflow Research

A research roadmap was presented by Deborah Grzybowski, Ph.D, Assistant Professor of Ophthalmology and Biomedical Engineering at the Ohio State University in Columbus, OH and a course director for the Neural Hydrodynamics Symposium. The research is being jointly lead by Dr. Steven Katz, Associate Professor of Ophthalmology at Ohio State, an IHRF Scientific Advisor and a fellow course director for the NHD Symposium.

There is limited knowledge about CSF physiology, especially regarding the areas and mechanisms of fl uid movement from the subarachnoid space. Dr. Gryzbowski and Dr. Katz hypothesize that an increase in intracranial pressure is caused by increased resistance at the pia-arachnoid cell layer in the arachnoid granulations, the tiny channels that drain CSF into the cerebral blood circulation. In other words, CSF outflow resistance in the pia-arachnoid cells could be what causes intracranial hypertension.

To determine whether this theory is true, Drs. Gryzbowski and Katz have undertaken a multi-faceted approach to identify proteins and receptors
that might influence CSF outfl ow. They proposed both clinical and basic science research. Clinical projects, in collaboration with the IH Registry, include a genetic study of IIH patients, who have at least two family members with the disorder.

A second project will analyze levels of Vitamin A and its analogues, transport proteins, specific receptors, and obesity regulation proteins and hormones in both CSF and blood serum of IIH patients. A third clinical project will study fluid movement of pre- and post-shunt IIH patients, using a diffusion tensor MRI scan to measure whether brain edema and increased diff usion are factors in IIH.

Drs. Gryzbowski and Katz have already accomplished one of their basic science goals by successfully growing human pia-arachnoid cells in their lab for the first time in history. This achievement will significantly clarify the role of these cells in CSF outflow.

Additionally, basic science projects include brain mapping of the arachnoid granulations and villi; studying the role of Vitamin A and its eff ect on CSF outflow, as well as identifying specific proteins and receptors (carbonic anhydrase, somatostatin, alpha-adrenergic, beta-adrenergic and the Vitamin A transduction pathway) that infl uence outfl ow; and the development of ex vivo and in vitro CSF outflow models.